The aim of this proposal is to organize a conference titled "Ubiquitin and Cancer: From Molecular Targets and Mechanisms to the Clinic" scheduled for January 18-22, 2006, at Disney's Contemporary Resort in Lake Buena Vista, Florida. [unreadable] [unreadable] This conference is unique among other meetings in the protein ubiquitylation field for its strong clinical/translational component (1/3 of all talks), including the opportunity to review the recent successes with proteasome.inhibitors in treating cancer in the clinic, as well as the pre-clinical studies validating ubiquitin ligase inhibitors for cancer therapy. Thus, there will be little overlap with other planned meetings on the UPS because of its more focused program, with respect both to the cell biology processes and to the disease that will be covered. [unreadable] [unreadable] Specifically, the meeting objectives are: 1) to provide an overview of the field of protein ubiquitylation, including review and discussion of the UPS-mediated regulation of various cellular processes that are relevant for cancer; 2) to foster discussions on the role of the UPS in malignancy and the opportunities for therapeutic intervention (drug targets); 3) to evaluate the successes and limitations of existing as well as proposed therapeutic approaches to interfere with the UPS; 4) to provide a forum for interaction among cancer scientists and experts in the field of protein ubiquitylation; 5) to contribute to the education of young scientists and others interested in the fields of cancer and the UPS. [unreadable] [unreadable] The field of protein ubiquitylation and degradation has experienced explosive growth in the past decade. The UPS regulates an enormous range of biological processes, including cell cycle, apoptosis, protein trafficking, signaling, DMA replication and repair, and angiogenesis. Consistently, defects in the UPS have already been directly implicated with many diseases. Deregulated protein ubiquitylation represents a major contributing factor for cancer development. Well known examples are the deregulation of the ubiquitin ligases BRCA1, Mdm2, VHL and Skp2 in various cancers. We expect that this meeting will foster extensive discussion on therapeutic opportunities, on therapeutic approaches and on the role of the UPS in malignancy. Emphasis will be given to the challenges involved in target identification and validation, and in drug development. [unreadable] [unreadable] [unreadable]